Lingual tuberculosis mimicking malignant lesion: A rare manifestation of a common disease

We report a rare case of tuberculosis (TB) of base of the tongue following pulmonary TB. Patient presented to us with chief complaints of sore throat, dysphagia, and hoarseness of voice for 20 days. Examination with 90° telescope revealed ulcerative lesion in the base of the tongue on the left side of size 0.5 cm and another lesion in the left arytenoid and inter arytenoid area extending to the false vocal cord of the left side with undermined edges along with whitish slough at the center of the ulcer. Infection of the oral cavity with Mycobacterium tuberculosis is rare, however, it should be considered among the differential diagnosis of the lesions of the oral cavity. The biopsy is necessary to confirm the diagnosis

Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic

GRN mutations cause frontotemporal dementia (GRN-FTD) due to deficiency in progranulin (PGRN), a lysosomal and secreted protein with unclear function. Here, we found that Grn-/- mice exhibit a global deficiency in bis(monoacylglycero)phosphate (BMP), an endolysosomal phospholipid we identified as a pH-dependent PGRN interactor as well as a redox-sensitive enhancer of lysosomal proteolysis and lipolysis. Grn-/- brains also showed an age-dependent, secondary storage of glucocerebrosidase substrate glucosylsphingosine. We investigated a protein replacement strategy by engineering protein transport vehicle (PTV):PGRN-a recombinant protein linking PGRN to a modified Fc domain that binds human transferrin receptor for enhanced CNS biodistribution. PTV:PGRN rescued various Grn-/- phenotypes in primary murine macrophages and human iPSC-derived microglia, including oxidative stress, lysosomal dysfunction, and endomembrane damage. Peripherally delivered PTV:PGRN corrected levels of BMP, glucosylsphingosine, and disease pathology in Grn-/- CNS, including microgliosis, lipofuscinosis, and neuronal damage. PTV:PGRN thus represents a potential biotherapeutic for GRN-FTD